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Safety and Immunogenicity of a Candidate RVFV Vaccine (RVF001)

Primary Purpose

Rift Valley Fever

Status
Completed
Phase
Early Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
ChAdOx1 RVF
Sponsored by
University of Oxford
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Rift Valley Fever focused on measuring RVF, ChAdOx1, vaccine

Eligibility Criteria

18 Years - 50 Years (Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

The volunteer must satisfy all the following criteria to be eligible for the study:

  1. Healthy adults aged 18 to 50 years
  2. Able and willing (in the Investigator's opinion) to comply with all study requirements
  3. Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner or access this medical history electronically
  4. For females only, willingness to practice continuous effective contraception for at least 3 months and a negative pregnancy test on the day(s) of screening and vaccination
  5. Agreement to refrain from blood donation during the course of the study
  6. Able to provide written informed consent

Exclusion Criteria:

The volunteer may not enter the study if any of the following apply:

  1. Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period
  2. Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data.
  3. Prior receipt of any vaccines administered ≤30 days before enrolment and/or planned receipt of a vaccine ≤30 days after enrolment EXCEPT for protein, RNA (or other non-adenovirus based) COVID-19 vaccinations which may be given within 14 days of the trial vaccine.
  4. Receipt of a recombinant simian adenoviral vaccine prior to enrolment
  5. Planned receipt of another adenoviral vectored vaccine (e.g. Oxford/Astrazeneca or Janssen COVID-19 vaccines) within 90 days after the vaccination with the ChAdOx1 RVF
  6. Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate
  7. Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed)
  8. COVID-19 infection diagnosed in the community in the 28 days prior to enrolment
  9. Any main covid-19 symptom within 28 days of enrolment:

    1. Fever (subjective or ≥37.8)
    2. New continuous cough
    3. Loss of sense of smell
    4. Loss of sense of taste
  10. Clinical suspicion of acute COVID-19 in the 28 days prior to enrolment
  11. History of allergic disease or reactions likely to be exacerbated by any component of the vaccine
  12. Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema.
  13. Any history of anaphylaxis in relation to vaccination
  14. Pregnancy, lactation or willingness/intention to become pregnant during the study
  15. History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ)
  16. History of serious psychiatric condition likely to affect participation in the study
  17. Bleeding disorder (eg. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture
  18. Any other serious chronic illness requiring hospital specialist supervision
  19. Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week
  20. Suspected or known injecting drug abuse in the 5 years preceding enrolment
  21. Seropositive for hepatitis B surface antigen (HBsAg)
  22. Seropositive for hepatitis C virus (antibodies to HCV)
  23. Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis
  24. Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data
  25. Inability of the study team to contact the volunteer's GP (or access summary care record, if available) to confirm medical history and safety to participate
  26. Prior natural exposure to RVFV as determined by seropositivity for RVFV antigens by ELISA and neutralizing antibody assay (serology will be requested at the discretion of the investigator)
  27. History of confirmed major thrombotic event (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism), history of antiphospholipid syndrome, or history of heparin induced thrombocytopenia

Sites / Locations

  • CCVTM, University of Oxford, Churchill Hospital

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

Experimental

Experimental

Experimental

Arm Label

Low dose

Medium dose

High dose

Arm Description

5 x 10^9 vp ChAdOx1 RVF delivered intramuscularly

2.5 x 10^10 vp ChAdOx1 RVF delivered intramuscularly

5 x 10^10 vp ChAdOx1 RVF delivered intramuscularly

Outcomes

Primary Outcome Measures

To assess local reactogenicity
Occurrence of solicited local reactogenicity signs and symptoms
To assess systemic reactogenicity
Occurrence of solicited systemic reactogenicity signs and symptoms
To assess unsolicited adverse events
Occurrence of unsolicited adverse events
To assess the safety and tolerability of ChAdOx1 RVF in healthy adult volunteers
Frequency of participants with clinically significant changes from baseline safety laboratory measures (haematology and biochemistry blood results)
To assess serious adverse events
Occurrence of serious adverse events

Secondary Outcome Measures

Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
ELISA to quantify antibodies to GnGc proteins
Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
RVFV neutralising antibody titres
Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
Ex vivo ELISpot and flow cytometry responses to GnGc

Full Information

First Posted
February 5, 2021
Last Updated
May 17, 2023
Sponsor
University of Oxford
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1. Study Identification

Unique Protocol Identification Number
NCT04754776
Brief Title
Safety and Immunogenicity of a Candidate RVFV Vaccine (RVF001)
Official Title
A Phase I Study to Determine the Safety & Immunogenicity of the Candidate Rift Valley Fever Virus (RVFV) Vaccine ChAdOx1 RVF in UK Healthy Adult Volunteers
Study Type
Interventional

2. Study Status

Record Verification Date
April 2022
Overall Recruitment Status
Completed
Study Start Date
June 11, 2021 (Actual)
Primary Completion Date
April 6, 2022 (Actual)
Study Completion Date
April 6, 2022 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Oxford

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Phase I open label, non-randomised dose escalation study on healthy UK volunteers aged from 18 to 50 years to assess the safety and immunogenicity of ChAdOx1 RVF
Detailed Description
The purpose of this study is to test a new vaccine against the Rift Valley Fever Virus (RVFV) in healthy volunteers. Rift Valley fever is a disease caused by RVFV and it is transmitted to humans through a mosquito bite or contact with virus-contaminated tissues and fluids. Although initially restricted to Africa, the virus can be transmitted by several different mosquito species that are more widely distributed than the virus itself, leading to concerns of disease spread as has occurred in the Arabian Peninsula and Madagascar. In humans, RVFV infection usually presents as a sudden febrile illness, but severe manifestations including bleeding disorders and neurological complications may also occur. RVFV is considered a global health threat with significant potential for international spread and use in bioterrorism. Vaccines against RVFV are available for livestock, however no licensed vaccines or specific treatments are currently available for humans. The study will enable assessment of the safety of the new vaccine called ChAdOx1 RVF and the extent of immune response in healthy volunteers. Healthy adult volunteers will receive a single dose of a new candidate vaccine at different doses. The objective of this first-in-human study is to find the optimal dose of the vaccine, balancing immune responses and profile of adverse events. Healthy volunteers aged 18-50 will be recruited in Oxford and vaccinated at the Centre for Clinical Vaccinology and Tropical Medicine and will be followed for a period of 3 months. The study is funded by the UK Biotechnology and Biological Sciences Research Council(BBSRC) and the Medical Research Council (MRC)/Department of Health, through the UK Vaccines Network.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Rift Valley Fever
Keywords
RVF, ChAdOx1, vaccine

7. Study Design

Primary Purpose
Treatment
Study Phase
Early Phase 1
Interventional Study Model
Sequential Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Low dose
Arm Type
Experimental
Arm Description
5 x 10^9 vp ChAdOx1 RVF delivered intramuscularly
Arm Title
Medium dose
Arm Type
Experimental
Arm Description
2.5 x 10^10 vp ChAdOx1 RVF delivered intramuscularly
Arm Title
High dose
Arm Type
Experimental
Arm Description
5 x 10^10 vp ChAdOx1 RVF delivered intramuscularly
Intervention Type
Biological
Intervention Name(s)
ChAdOx1 RVF
Intervention Description
Single dose of ChAdOx1 RVF
Primary Outcome Measure Information:
Title
To assess local reactogenicity
Description
Occurrence of solicited local reactogenicity signs and symptoms
Time Frame
7 days following vaccination
Title
To assess systemic reactogenicity
Description
Occurrence of solicited systemic reactogenicity signs and symptoms
Time Frame
7 days following vaccination
Title
To assess unsolicited adverse events
Description
Occurrence of unsolicited adverse events
Time Frame
28 days following vaccination
Title
To assess the safety and tolerability of ChAdOx1 RVF in healthy adult volunteers
Description
Frequency of participants with clinically significant changes from baseline safety laboratory measures (haematology and biochemistry blood results)
Time Frame
Duration of study (6 months)
Title
To assess serious adverse events
Description
Occurrence of serious adverse events
Time Frame
Duration of study (6 months)
Secondary Outcome Measure Information:
Title
Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
Description
ELISA to quantify antibodies to GnGc proteins
Time Frame
Duration of study (6 months)
Title
Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
Description
RVFV neutralising antibody titres
Time Frame
Duration of study (6 months)
Title
Assess the cellular and humoral immunogenicity of ChAdOx1 RVF in healthy adult volunteers
Description
Ex vivo ELISpot and flow cytometry responses to GnGc
Time Frame
Duration of study (6 months)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
50 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: The volunteer must satisfy all the following criteria to be eligible for the study: Healthy adults aged 18 to 50 years Able and willing (in the Investigator's opinion) to comply with all study requirements Willing to allow the investigators to discuss the volunteer's medical history with their General Practitioner or access this medical history electronically For females only, willingness to practice continuous effective contraception for at least 3 months and a negative pregnancy test on the day(s) of screening and vaccination Agreement to refrain from blood donation during the course of the study Able to provide written informed consent Exclusion Criteria: The volunteer may not enter the study if any of the following apply: Participation in another research study involving receipt of an investigational product in the 30 days preceding enrolment, or planned use during the study period Prior receipt of an investigational vaccine likely to impact on interpretation of the trial data. Prior receipt of any vaccines administered ≤30 days before enrolment and/or planned receipt of a vaccine ≤30 days after enrolment EXCEPT for protein, RNA (or other non-adenovirus based) COVID-19 vaccinations which may be given within 14 days of the trial vaccine. Receipt of a recombinant simian adenoviral vaccine prior to enrolment Planned receipt of another adenoviral vectored vaccine (e.g. Oxford/Astrazeneca or Janssen COVID-19 vaccines) within 90 days after the vaccination with the ChAdOx1 RVF Administration of immunoglobulins and/or any blood products within the three months preceding the planned administration of the vaccine candidate Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV infection; asplenia; recurrent, severe infections and chronic (more than 14 days) immunosuppressant medication within the past 6 months (inhaled and topical steroids are allowed) COVID-19 infection diagnosed in the community in the 28 days prior to enrolment Any main covid-19 symptom within 28 days of enrolment: Fever (subjective or ≥37.8) New continuous cough Loss of sense of smell Loss of sense of taste Clinical suspicion of acute COVID-19 in the 28 days prior to enrolment History of allergic disease or reactions likely to be exacerbated by any component of the vaccine Any history of hereditary angioedema, acquired angioedema, or idiopathic angioedema. Any history of anaphylaxis in relation to vaccination Pregnancy, lactation or willingness/intention to become pregnant during the study History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ) History of serious psychiatric condition likely to affect participation in the study Bleeding disorder (eg. factor deficiency, coagulopathy or platelet disorder), or prior history of significant bleeding or bruising following IM injections or venepuncture Any other serious chronic illness requiring hospital specialist supervision Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 units every week Suspected or known injecting drug abuse in the 5 years preceding enrolment Seropositive for hepatitis B surface antigen (HBsAg) Seropositive for hepatitis C virus (antibodies to HCV) Any clinically significant abnormal finding on screening biochemistry or haematology blood tests or urinalysis Any other significant disease, disorder or finding which may significantly increase the risk to the volunteer because of participation in the study, affect the ability of the volunteer to participate in the study or impair interpretation of the study data Inability of the study team to contact the volunteer's GP (or access summary care record, if available) to confirm medical history and safety to participate Prior natural exposure to RVFV as determined by seropositivity for RVFV antigens by ELISA and neutralizing antibody assay (serology will be requested at the discretion of the investigator) History of confirmed major thrombotic event (including cerebral venous sinus thrombosis, deep vein thrombosis, pulmonary embolism), history of antiphospholipid syndrome, or history of heparin induced thrombocytopenia
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Adrian VS Hill, Prof
Organizational Affiliation
Jenner Institute
Official's Role
Principal Investigator
Facility Information:
Facility Name
CCVTM, University of Oxford, Churchill Hospital
City
Oxford
ZIP/Postal Code
OX3 7LE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No

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Safety and Immunogenicity of a Candidate RVFV Vaccine (RVF001)

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